Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock

Objective: To test the hypothesis that nonselective adsorption by a hydroph obic resin of cytokines and other proinflammatory mediators could improve 7 2-hr survival in a rabbit model of endotoxic shock. Design. Prospective, randomized, controlled animal trial. Setting: Animal care facility at a research institution. Subjects: A total of 109 New Zealand white male rabbits. Interventions: Anesthetized rabbits were cannulated with indwelling femoral arterial and venous lines. Septic shock was induced by a single intravenou s injection of Escherichia coli lipopolysaccharide, The dose was experiment ally assessed in 40 rabbits receiving 1.0, 0.5, 0.1, and 0.05 mg/kg body we ight to determine LD80 at 72 hrs, Extracorporeal circulation consisted of p lasma filtration coupled with passage of the plasma filtrate through a hydr ophobic sorbent and reinfusion into the venous line, The extracorporeal tre atment lasted for 3 hrs, Rabbits injected with endotoxin (0.05 mg/kg) were submitted to plasma filtration with (19 rabbits) or without (20 rabbits) so rbent adsorption, As controls, rabbits injected with vehicle alone were tre ated with plasma filtration (ten rabbits) or without (ten rabbits) sorbent adsorption. Ten rabbits were monitored under anesthesia to determine basal survival. Measurements and Main Results: Plasma concentrations of endotoxin, bioactiv e tumor necrosis factor, resin-adsorbed platelet-activating factor, mean ar terial pressure, base excess, and white cell count were assessed and a glob al severity score was established. At 72 hrs, cumulative survival was signi ficantly (p = .0041) improved in septic rabbits treated with coupled plasma filtration-adsorption. Circulating tumor necrosis factor bioactivity remai ned similar in control and treated rabbits. Biologically significant amount s of platelet activating factor were eluted from the sorbent during the ent ire treatment time. The severity score inversely correlated with survival ( p < .001). Conclusions: Coupled plasma filtration-adsorption improved survival in a ra bbit model of endotoxic shock, Coupled plasma filtration-adsorption may be an extracorporeal treatment capable of removing structurally different infl ammatory mediators associated with sepsis.